Cooperative Interaction between the Alpha1-Adrenoceptors (α1-AR) and Transient Receptor Potential (TRP) Triggers a Proliferative Cell Signal in Prostate Cancer Cell Lines

Abstract

Calcium (Ca2+) increases the proliferation of human advanced prostate cancer (PCa) cells but the ion channels involved are unknown. Santoni and Quaglia groups investigated the correlation between alpha1D-adrenergic receptor (α1D-AR) and the transient receptor potential vanilloid type 1 (TRPV1) ion channel expression in PCa cells. The α1D-AR and TRPV1 mRNAs are increased in PCa compared to BPH. α1D-AR and TRPV1 are co-expressed in PCa cells. Norepinephrine (NE) induced α1D-AR-and TRPV1-dependent protons release, Ca2+ flux in PC3 cells and activation of PLC, PKC and ERK path-ways that stimulated PC3 cell proliferation. Similarly, a role for TRPC6 or GPR55 in α1-AR-dependent proliferation of mesangial cells and PCa cells was reported.Overall, a crosstalk between α1-AR and TRPs in PCa cells, involved in the control of cell proliferation has been demonstrated. These data strongly promote a putative novel pharmacological approach in the treatment of PCa by targeting both α1-AR and TRP channels.

TRPC channels: Structure, function, regulation and recent advances in small molecular probes

“…Functional TRPC6 channels are found to be overexpressed in prostate, stomach, breast cancers, as well as neuroglia, as compared to the low or undetectable levels in the corresponding normal tissues. Recent studies have demonstrated [Ca 2+ ] c rise mediated via activation of α1-adrenoceptors in normal mesangial cells and prostate cancer cells, which elicits a proliferative signal, implicating the control in cell proliferation (Santoni et al, 2015). In prostate cancer mouse model of knock-In mouse adenocarcinoma prostate (KIMAP), dietary supplement of high Ca 2+ accelerated the progression of prostate tumors in a manner that involves increasing the expression of calcium sensing receptor and TRPC6, an effect that was attenuated through dietary supplement of Vitamin D3.…”